This proposed five year training program is designed to expand the applicant's knowledge in advanced molecular biology. The primary goals of the training program are to expand the applicant's ability in performing basic research into a hypothesis-driven, mechanistic understanding of tumorigenesis, and to provide her with the skills necessary to develop a productive, independently funded, laboratory. To accomplish these goals, a rigorous training program has been proposed, including didactic instruction in advanced molecular biology, fundamental instruction in the conduct of clinical investigation, and a research experience focusing on advanced laboratory techniques. The training program has been thoughtfully constructed to help the applicant achieve her long term career goal of the investigation of novel treatment strategies for neuroblastoma. The research program incorporates several unique aspects available at the University of Florida, namely the University of Florida Shands Cancer Center with expertise of a number of scientists in the field of cancer research, and the Department of Surgery Cancer Research Laboratory with its pioneering discoveries in the biology of focal adhesion kinase (FAK). The proposed research focuses on the expression and function of FAK in neuroblastoma, a childhood tumor with a dismal prognosis. This proposal builds upon preliminary data demonstrating a correlation between FAK expression and MYCN oncogene amplification, and the effects of attenuation of FAK upon cellular survival. We hypothesize that FAK is overexpressed in neuroblastomas with MYCN amplification and that MYCN is involved in the transcriptional regulation of FAK. We will study FAK expression in human neuroblastoma tissue samples and cell lines, measure the effects of FAK upon cellular attachment, proliferation, motility, and survival, and determine the effects of FAK inhibition upon tumor growth and survival in an in vivo model of neuroblastoma. Better insight into the relationship between FAK and MYCN offers the potential for translating this knowledge into clinically relevant therapies for this devastating childhood tumor. [unreadable] [unreadable] [unreadable]